Document Detail

IL-33-responsive lineage- CD25+ CD44(hi) lymphoid cells mediate innate type 2 immunity and allergic inflammation in the lungs.
MedLine Citation:
PMID:  22198948     Owner:  NLM     Status:  MEDLINE    
Innate immunity provides the first line of response to invading pathogens and a variety of environmental insults. Recent studies identified novel subsets of innate lymphoid cells that are capable of mediating immune responses in mucosal organs. In this paper, we describe a subset of lymphoid cells that is involved in innate type 2 immunity in the lungs. Airway exposure of naive BALB/c or C57BL/6J mice to IL-33 results in a rapid (<12 h) production of IL-5 and IL-13 and marked airway eosinophilia independently of adaptive immunity. In the lungs of nonsensitized naive mice, IL-33-responsive cells were identified that have a lymphoid morphology, lack lineage markers, highly express CD25, CD44, Thy1.2, ICOS, Sca-1, and IL-7Rα (i.e., Lin(-)CD25(+)CD44(hi) lymphoid cells), and require IL-7Rα for their development. Airway exposure of naive mice to a clinically relevant ubiquitous fungal allergen, Alternaria alternata, increases bronchoalveolar lavage levels of IL-33, followed by IL-5 and IL-13 production and airway eosinophilia without T or B cells. This innate type 2 response to the allergen is nearly abolished in mice deficient in IL-33R (i.e., ST2), and the Lin(-)CD25(+)CD44(hi) lymphoid cells in the lungs are required and sufficient to mediate the response. Thus, a subset of innate immune cells that responds to IL-33 and vigorously produces Th2-type cytokines is present in mouse lungs. These cells may provide a novel mechanism for type 2 immunity in the airways and induction of allergic airway diseases such as asthma.
Kathleen R Bartemes; Koji Iijima; Takao Kobayashi; Gail M Kephart; Andrew N McKenzie; Hirohito Kita
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-23
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  188     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-20     Completed Date:  2012-06-11     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1503-13     Citation Subset:  AIM; IM    
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MeSH Terms
Allergens / immunology
Alternaria / immunology
Antigens, CD44
Cell Lineage
Immunity, Innate* / immunology
Interleukin-2 Receptor alpha Subunit
Interleukins / immunology*
Lymphocytes / immunology*
Pneumonia / immunology*
Respiratory Hypersensitivity / immunology
Th2 Cells / immunology
Grant Support
MC_U105178805//Medical Research Council; R01 AI034486/AI/NIAID NIH HHS; R01 AI034486-15/AI/NIAID NIH HHS; R01 AI049235/AI/NIAID NIH HHS; R01 AI049235-10/AI/NIAID NIH HHS; R01 AI071106/AI/NIAID NIH HHS; R01 AI071106-05/AI/NIAID NIH HHS; R01 AI34486/AI/NIAID NIH HHS; R01 AI49235/AI/NIAID NIH HHS
Reg. No./Substance:
0/Allergens; 0/Antigens, CD44; 0/Interleukin-2 Receptor alpha Subunit; 0/Interleukins; 0/interleukin-33, mouse

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